Efficacy and safety of early‐start deferiprone in infants and young children with transfusion‐dependent beta thalassemia: Evidence for iron shuttling to transferrin in a randomized, double‐blind, placebo‐controlled, clinical trial (START)

Abstract

AbstractChildren with transfusion‐dependent thalassemia (TDT) require regular blood transfusions that, without iron‐chelation therapy, lead to iron‐overload toxicities. Current practice delays chelation therapy (late‐start) until reaching iron overload (serum ferritin ≥1000 μg/L) to minimize risks of iron‐depletion. Deferiprone's distinct pharmacological properties, including iron‐shuttling to transferrin, may reduce risks of iron depletion during mild‐to‐moderate iron loads and iron overload/toxicity in children with TDT. The early‐start deferiprone (START) study evaluated the efficacy/safety of early‐start deferiprone in infants/young children with TDT. Sixty‐four infants/children recently diagnosed with beta‐thalassemia and serum ferritin (SF) between 200 and 600 μg/L were randomly assigned 1:1 to receive deferiprone or placebo for 12 months or until reaching SF‐threshold (≥1000 μg/L at two consecutive visits). Deferiprone was initiated at 25 mg/kg/day and increased to 50 mg/kg/day; some recipients' dosages increased to 75 mg/kg/day based on iron levels. The primary endpoint was the proportion of patients ≥SF‐threshold by month 12. Monthly transferrin saturation (TSAT) assessment evaluated iron‐shuttling. At baseline, there was no significant difference in mean age (deferiprone: 3.03 years, placebo: 2.63 years), SF (deferiprone: 513.8 μg/L, placebo: 451.7 μg/L), or TSAT (deferiprone: 47.98%, placebo: 43.43%) between groups. At month 12, there was no significant difference in growth or adverse event (AE) rates between groups. No deferiprone‐treated patients were iron‐depleted. At month 12, 66% of patients receiving deferiprone remained below SF threshold versus 39% of placebo (p = .045). Deferiprone‐treated patients showed higher TSAT levels and reached ≥60% TSAT threshold faster. Early‐start deferiprone was well‐tolerated, not associated with iron depletion, and efficacious in reducing iron overload in infants/children with TDT. TSAT results provide the first clinical evidence of deferiprone shuttling iron to transferrin.